Environmental Factor, December 2010, National Institute of Environmental Health Sciences

Nel delivers nano lecture

By Thaddeus Schug December 2010

Nel is director of the Center for the Environmental Impact of Nanotechnology and the NIEHS-funded Center for Nanobiology and Predictive Toxicology, both of which are based at UCLA.
(Photo courtesy of Steve McCaw)

"Nanomaterials are increasingly coming into contact with people and the environment, and understanding how they interact with biological systems is essential to ensure their safe use," maintains NIEHS grantee Andre Nel, M.D., Ph.D. Nel, who is a Professor and Chief of NanoMedicine at the University of California, Los Angeles (UCLA), spoke on "Nanotoxicology as a Predictive Science: From Cells to Whole Animals," at the Keystone Science Lecture Seminar Series Nov. 17.

Nanotechnology has been a rapidly developing field over the past decade, but very little research exists about how the tiny particles may impact human health and safety. "Nanotechnology and engineered nanomaterials (ENMs) have lead to rapid advancements in medicine, engineering, and biotechnology," said Nel.

"The challenge for us is to use [lessons from] the problems encountered through the use of industrial chemicals to prevent environmental health and safety problems from the implementation of nanotechnology. This is an enormous challenge because of the rapid pace of nanotechnology development," Nel added.

Nel explained how he and his colleagues at The Center for Environmental Implications of Nanotechnology (CEIN) as well as the Center for Nanobiology and Predictive Toxicology at UCLA investigate how a range of potentially new properties such as size, shape, structure, and reactive surface may influence ENM behavior in biological systems.

"We use a systems biology approach to understand how this wide range of properties at the level of molecules and cells could lead to adverse biological responses that may predict their impact on human health and more complicated organisms in the environment," Nel explained.

Developing a predictive science for nano safety

According to Nel, the novel size and unique chemical and physical properties of nanomaterials provide for an endless number of biological integrations. To deal with these complexities, Nel and his colleagues have been developing sophisticated high-throughput screening technology that allows for high capacity data generation.

"The idea is that we can use predictions, coming from these studies to identify those materials that could pose a hazard in humans and more complicated life forms in the environment, to allow us to prioritize in vivo testing, which cannot serve as the primary test platform due to cost and time," said Nel.

Nel utilizes an organized workflow plan, which he referred to as the "key ingredients needed to establish a predictive science at the nano-bio interface." The first phase is to synthesize nanomaterial libraries with unique properties and to develop detailed characterization of those materials and their properties using technology such as electron microscopy, x-ray diffraction analysis, zeta potential and dynamic light scattering. Next, they develop and implement the appropriate biological assays and computational analyses needed to predict and rank hazard potential through cellular high throughput screening before prioritizing which materials should be tested in animal systems. Finally, these predictions are validated in whole animal systems (see text box).

Nel concluded his talk by saying, "Because of the relative lack of knowledge of these new materials and the potential adverse effects on human health and safety, now is the opportune time to launch the research and decision-making tools to ensure safe implementation of this new scientific field."

"Andre is really at the forefront of developing in vitro modeling systems that can be effectively used to screen and predict for potential harmful effects of nanomaterials," Sri Nadadur, Ph.D., a health scientist administrator in the NIEHS Division of Extramural Research and Training, and organizer of the lecture. Nadadur added, "We are excited to have Andre's expertise in predictive modeling as part of our newly-funded nano consortium (see story (http://www.niehs.nih.gov/news/newsletter/2010/december/science-kick.cfm)).

(Thaddeus Schug, Ph.D., is a postdoctoral research fellow in the NIEHS Laboratory of Signal Transduction and a regular contributor to the Environmental Factor. He is currently on detail as a program analyst in the NIEHS Division of Extramural Research and Training.)

Proof of principle for a predictive modeling system

Nel described experiments his group conducted to determine toxicity of nanoscale metal oxides. Following detailed characterization and performance of in vitro assays, materials posing toxicity were tested in zebrafish embryos and in rodents, which underwent pulmonary exposure. Nel presented data showing that the major classes of metal and metal oxides that pose danger at the cellular level also exert effects on hatching success, survival, and the development of morphological abnormalities in zebrafish, as well as generation of pulmonary inflammation in mice.

Nel showed how the observations made during in vitro experiments correlated with, and deviated from, those shown in the whole animal. The data illustrate that it is possible to use in vitro hazard ranking as determined by heatmaps and self-organizing maps and to test those predictions in whole animals with some measure of success, but also demonstrate differences in the behavior of mammalian cells and zebrafish in their response to nano-silver.

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